The critical role of novel benzophenone analogs on tumor growth inhibition targeting angiogenesis and apoptosis

Abstract

In modern biology, one of the major importance is the progress of anti-cancer drugs with specific targets. The angiopreventive and in vitro tumor inhibition activities of novel synthetic benzophenone analogs were given more attention and explored in a very professional way. The multistep synthesis of novel benzophenone analogs (9a-d and 10a-d) allowing substitution with methyl, choloro and flouro groups at different positions on the identical chemical backbone and the variations in the number of substituents were synthesized and characterized. In this study, we further evaluated the newly synthesized compounds for cytotoxic and anti-proliferative effects against the A549, HeLa and MCF-7 cells. For anti-angiogenic effects, further assessments were made for the potent lead compound. Through structure activity relationship, we found that an increase in the number of methyl, chloro and fluoro groups in a ring of benzophenone on compound 9d resulted in higher potency compared to other compounds. The tumor inhibition was importantly suppressed and reflected by the neovessel formation in in vivo systems, such as the CAM. Compound 9d interacts with rVEGF by hydrogen bond in-silico, thereby down regulates the VEGF expression in angiogenesis. Through the investigation, it is suggested that the compound 9d on clonogenesis and cell migration assays have the potency to exhibit the prolonged activity with cell cycle arrest on G2/M phase against cancer progression. In addition to that, through caspase activated DNase mediated apoptosis the compound 9d inhibit A549 cells.

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